Table 2

Characteristics of Warfarin and Nonvitamin K-Dependent Oral Anticoagulant Agents

WarfarinApixabanRivaroxabanDabigatranEdoxaban
Renal clearance of parent drug<1%27%36%80%50%
Removal with 4 h of hemodialysis<1%7%<1%50%–60%9%
Volume of distribution, l (66)8215050–10107
Reversal agentVitamin K, FFP, 4F-PCC4F-PCC4F-PCCIdarucizumab4F-PCC
Lowest CrCl drug can be prescribed per FDA label, ml/minCan be used on dialysis<15151515
HR (95% CI) of stroke referent to warfarin, CrCl <50 ml/minReference0.79 (0.55–1.14)0.88 (0.65–1.19)0.56 (0.37–0.85)0.87 (0.65–1.18)
HR (95% CI) of major bleeding referent to warfarin, CrCl <50 ml/minReference0.50 (0.38–0.66)0.98 (0.84–1.14)1.01 (0.79–1.30)0.76 (0.58–0.98)

CI = confidence interval; CrCl = creatinine clearance; FDA = U.S. Food and Drug Administration; FFP = fresh-frozen plasma; 4F-PCC = 4-factor prothrombin complex concentrate; HR = hazard ratio.

  • A 5-mg twice-daily dose of apixaban is suggested for patients with CrCl <15 ml/min. This dosing suggestion was based on a small single-dose pharmacokinetic and pharmacodynamic (anti-Xa activity) study. Clinical efficacy and long-term safety studies have not been done in this population; therefore, use apixaban with caution in patients with advanced or end-stage chronic kidney disease.

  • 30–50 ml/min for the comparison of edoxaban versus warfarin (37).